Search

NEWAGE is a direction-sensitive dark matter search experiment with a three-dimensional tracking detector based on a gaseous micro time projection chamber. A direction-sensitive dark matter search was carried out at Kamioka Observatory with a total live time of 318.0 days resulting in an exposure of 3.18 kg$\cdot$days. A new gamma-ray rejection and a head-tail determination analysis were implemented for this work. No significant non-isotropic signal from the directional analysis was found and a 90% confidence level upper limit on spin-dependent WIMP-proton cross section of 25.7 pb for WIMP mass of 150 GeV/c2 was derived. This upper limit is the most stringent in the direction-sensitive dark matter searches., Comment: submitted to PTEP

Background The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. Methods This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71–75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. Discussion If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. Trial registration Registry number: jRCTs031200099. Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020.

Background: There will be significant changes in the diagnosis of IDH-wildtype adult-type gliomas in the upcoming 5th edition of the WHO Classification of Central Nervous System Tumours. IDH-wildtype lower grade gliomas (IDHwt LGGs) that harbor molecular features of glioblastoma (EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7+/10-), or TERT promoter mutations) will be diagnosed as glioblastomas (GBMs), while IDH-wildtype astrocytomas will not be included as a separate tumor type. However, IDHwt LGGs are a very heterogeneous group of tumors, and further investigation is warranted particularly in those without molecular features of glioblastoma. To elucidate the biology of IDHwt LGGs, we analyzed DNA methylation profile and survival time. Materials and Methods: Of the 724 adult-type diffuse glioma samples from a multi-institutional study, 64 IDHwt LGG, including 54 without any of molecular features of GBM and 10 with PDGFRA amplification or TERT promoter mutation, were examined using Infinium MethylationEPIC BeadChip. The raw data files (IDAT files) were analyzed by the web-based DNA methylation classifier provided by DKFZ (MolecularNeuropathology.org) or by R (Version 4.0.4) using the minfi (1.34.0) and Rtsne (0.15) packages. [Result] Twenty-three out of 54 IDHwt LGGs matched known methylation classes using the DKFZ methylation classifier. In t-Distributed Stochastic Neighbor Embedding clustering analysis, 20 cases formed a cluster within the methylation class family glioblastoma, IDH-wildtype, mainly subclass RTK I (“GBM” cluster). Another 29 IDHwt LGGs formed an independent cluster (“LGG” cluster) separate from any of the existing reference groups near but not overlapping with several subtypes of pediatric-type lower grade gliomas. The “LGG” cluster cases had significantly longer overall survival than the “GBM” cluster cases. Discussion: Methylation profiling showed that IDHwt LGGs without molecular features of GBM were heterogeneous group of tumors. Our data suggested the presence of “true” IDHwt LGGs with intermediate prognosis.

Additional file 1: Supplemental information. C11orf95-RELA fusion drives aberrant gene expression through the unique epigenetic regulation for ependymoma formation. atsuya Ozawa, Syuzo Kaneko, Frank Szulzewsky, Zhiwei Qiao, Mutsumi Takadera, Yoshitaka Narita, Tadashi Kondo, Eric C. Holland, Ryuji Hamamoto, Koichi Ichimura. Table of Contents:Supplementary Figures S1-S6; Supplementary Figure legends; Supplementary Table legends. (DOCX 142 KB)

Additional file 1. Supplementary materials and methods

Direction sensitivity could provide robust evidence for the direct detection of weakly interacting massive particles constituting dark matter. However, the sensitivity of this method remains low due to the radioactive backgrounds. The purpose of this study is to develop a low-background detector as a two-dimensional imaging device for a gaseous time projection chamber. In direction-sensitive dark matter experiments~(e.g. NEWAGE), $��$-rays emitted from the detector components often create substantial radioactive backgrounds. Based on the study of the background of NEWAGE, a new detector "low-$��$ $��$-PIC" is developed. The produced $��$-PIC performs well as a gas detector and the $��$-ray emission rate from the $��$-PIC reduced by a factor of 100.

The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

The scintillation yields of ZnWO$_4$ crystals change depending on the incident direction of particles. This property can be used as a direction-sensitive dark matter detector. So, we investigated the ZnWO$_4$ light yields ratio of neutron-induced nuclear recoils to gamma-ray induced electron recoils(quenching factor). Two surfaces almost perpendicular to the crystal axis of ZnWO$_4$ were irradiated with a quasi-monochromatic neutron beam of 0.885MeV, and the quenching factors of both surfaces for the oxygen-nucleus recoil in the ZnWO$_4$ crystal were measured. The obtained quenching factors of the two surfaces were 0.235 $\pm$ 0.026 and 0.199 $\pm$ 0.020, respectively confirming 15.3$\%$ of anisotropy.

Table S6. Univariate and multivariate analysis of ST and PF ependymomas in PFS and OS. (DOCX 44 kb)

Table S5. Validation results of PF-EPN subgroup prediction rule candidates. (DOCX 16 kb)

The Japan Pediatric Molecular Neuro-Oncology Group (JPMNG): participating centers and departments. (DOCX 17 kb)

BACKGROUND AND AIM: Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. METHODS: In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. RESULTS: By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P

We have observed a metal-insulator transition of a quasi-two dimensional electronic system in transition metal dichalcogenide $2H$-TaSe$_2$ caused by doping iron. The sheet resistance of $2H$-Fe$_x$TaSe$_2$ ($0 \leq x \leq 0.120$) single crystals rises about $10^6$ times with the increasing of $x$ at the lowest temperature. We investigated the temperature dependence of the resistance and found a metal-insulator transition with a critical sheet resistance $11.7 \pm 5.4$ k$\rm{\Omega}$. The critical exponent of the localization length $\nu$ is estimated $0.31 \pm 0.18$. The values of the critical sheet resistance and $\nu$ are accordant to those of the \textit{chiral unitary class} (less than $h/1.49e^2=17.3$ k$\rm{\Omega}$ and $0.35 \pm 0.03$, respectively). We suggest that $2H$-Fe$_x$TaSe$_2$ is classified as the chiral unitary class, not as standard unitary class., Comment: 10 pages, 4 figures

Distributions of molecular alterations according to histology in Cohort 1. Figure S2. Kaplan-Meier analysis for Group A cases stratified by 1p/19q status. Figure S3. Kaplan-Meier analyses for GBM cases in Cohorts 1 and 2. (PPTX 172Â kb)

Distributions of molecular alterations according to histology in Cohort 1. Figure S2. Kaplan-Meier analysis for Group A cases stratified by 1p/19q status. Figure S3. Kaplan-Meier analyses for GBM cases in Cohorts 1 and 2. (PPTX 172Â kb)

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies.

The main goal of the KamLAND reactor electron anti-neutrino experiment is a search for electron anti-neutrino oscillation using inverse-beta decay reaction in 1,000 ton of ultra-pure liquid scintillator. The data-set is 1490.8 days from Mar. 2002 to May 2007. The best-fit oscillation parameters are Delta m^{2}_{21} = 7.58^{+0.14}_{-0.13} (stat.) +/- 0.15 (syst.) x 10$^{-5} eV^{2} and tan^{2}theta_{12} = 0.56^{+0.10}_{-0.07} (stat.) ^{+0.10}_{-0.06} (syst.). The statistical significance for reactor electron anti-neutrino disappearance is 8.8 sigma, and an undistorted electron anti-neutrino energy spectrum is disfavored at > 5 sigma., Parallel talk at ICHEP08, Philadelphia, USA, July 2008. 4 pages, LaTeX, 3 eps figures

Simple Summary The optimal cut-offs for tumor markers in CNS germ cell tumors (GCTs) to specify non-germinomatous GCTs are under active investigation. This study investigated 162 cases with histopathological confirmation and tumor markers, including 77 cases with robust specimens obtained from tumor resection. This study demonstrates that tumor markers are elevated in germinomas and teratomas, especially HCG in germinomas and AFP in immature teratomas, emphasizing the clinical significance of tissue diagnosis. Similarly, some biopsy cases without malignant findings on histopathology demonstrated tumor marker elevations, highlighting the limitations of reliable tissue diagnosis from a diminutive specimen. This study concludes that an integrated diagnosis based on tumor markers and histopathology is the key to precise diagnosis and, therefore, the avoidance of over- or under-treatment. This study also invites novel questions regarding whether marker-positive germinomas or teratomas should be treated as intensively as malignant NGGCTs, as well as the optimal treatment strategy for marker-negative immature teratomas. The central nervous system germ cell tumor (CNS GCT) is a rare and incompletely understood disease. A major outstanding question in the 2015 consensus document for CNS GCT management was the utility and interpretation of the tumor markers human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) in the diagnosis of malignant non-germinomatous GCTs (hereafter NGGCTs) prior to treatment. In the current study, we assembled two geographically and ethnically different clinical cohorts from the Mayo Clinic (1988-2017) and the intracranial GCT Genome Analysis Consortium (iGCT Consortium) in Japan to address this question. Patients with both histopathological diagnosis and tumor markers available were eligible for inclusion (n = 162). Biopsy and surgical resection were performed in 85 and 77 cases, respectively. Among 77 resections, 35 demonstrated positivity for HCG, AFP, or both (45%). Seventeen of the marker-positive cases had no malignant non-germinomatous component identified on histopathology, but they were composed strictly of germinoma, teratoma, or both (49%). One embryonal carcinoma was the only marker-negative NGGCT in the study sample. Among 85 biopsies, 18 were marker positive (21%). Seven of these patients had no malignant non-germinomatous component on histopathology, suggesting the potential limitations of limited tissue sample volumes. Neither histopathological diagnosis nor tumor markers alone reliably diagnose NGGCTs due to the secretion of HCG and AFP by germinomas and teratomas. Treatment planning should incorporate integrated histopathological and laboratory-based diagnosis to optimize diagnostic and treatment strategies for this unusual and histologically heterogeneous tumor.